Cost-effectiveness of a community-delivered multicomponent intervention compared with enhanced standard care of obese adolescents: cost-utility analysis alongside a randomised controlled trial (the HELP trial)

OBJECTIVE: To undertake a cost-utility analysis of a motivational multicomponent lifestyle-modification intervention in a community setting (the Healthy Eating Lifestyle Programme (HELP)) compared with enhanced standard care. DESIGN: Cost-utility analysis alongside a randomised controlled trial. SETTING: Community settings in Greater London, England. PARTICIPANTS: 174 young people with obesity aged 12-19 years. INTERVENTIONS: Intervention participants received 12 one-to-one sessions across 6 months, addressing lifestyle behaviours and focusing on motivation to change and self-esteem rather than weight change, delivered by trained graduate health workers in community settings. Control participants received a single 1-hour one-to-one nurse-delivered session providing didactic weight-management advice. MAIN OUTCOME MEASURES: Mean costs and quality-adjusted life years (QALYs) per participant over a 1-year period using resource use data and utility values collected during the trial. Incremental cost-effectiveness ratio (ICER) was calculated and non-parametric bootstrapping was conducted to generate a cost-effectiveness acceptability curve (CEAC). RESULTS: Mean intervention costs per participant were £918 for HELP and £68 for enhanced standard care. There were no significant differences between the two groups in mean resource use per participant for any type of healthcare contact. Adjusted costs were significantly higher in the intervention group (mean incremental costs for HELP vs enhanced standard care £1003 (95% CI £837 to £1168)). There were no differences in adjusted QALYs between groups (mean QALYs gained 0.008 (95% CI -0.031 to 0.046)). The ICER of the HELP versus enhanced standard care was £120 630 per QALY gained. The CEAC shows that the probability that HELP was cost-effective relative to the enhanced standard care was 0.002 or 0.046, at a threshold of £20 000 or £30 000 per QALY gained. CONCLUSIONS: We did not find evidence that HELP was more effective than a single educational session in improving quality of life in a sample of adolescents with obesity. HELP was associated with higher costs, mainly due to the extra costs of delivering the intervention and therefore is not cost-effective. TRIAL REGISTRATION NUMBER: ISRCTN9984011

Respiratory muscle activity in voluntary breathing tracking tasks: Implications for the assessment of respiratory motor control

How the involuntary (bulbospinal) and voluntary (corticospinal) pathways interact in respiratory muscle control is not established. To determine the role of excitatory corticobulbar pathways in humans, studies typically compare electromyographic activity (EMG) or evoked responses in respiratory muscles during hypercapnic and voluntary tasks. Although ventilation is matched between tasks by having participants track signals of ventilation, these tasks may not result in matched respiratory muscle activity. The aim of this study was to describe respiratory muscle activity and ribcage and abdominal excursions during two different voluntary conditions, compared to hypercapnic hyperventilation. Ventilation was matched in the voluntary conditions via (i) a simple target of lung volume (‘volume tracking’) or (ii) targets of both ribcage and abdominal excursions, adjusted to end-expiratory lung volume in hypercapnic hyperventilation (‘bands tracking’). Compared to hypercapnic hyperventilation, respiratory parameters such as tidal volume were similar, but the ratio of ribcage to abdominal excursion was higher for both voluntary tasks. Inspiratory scalene and parasternal intercostal muscle activity was higher in volume tracking, but diaphragm and abdominal muscle activity showed little to no change. There were no differences in muscle activity in bands tracking for any muscle, compared to hypercapnic hyperventilation. An elevated ratio of ribcage to abdominal excursion in the bands tracking task indicates that participants could not accurately match the targets in this condition. Inspiratory muscle activity is altered in some muscles in some voluntary tasks, compared to hypercapnia. Therefore, differences in muscle activity should be considered in interpretation of studies that use these protocols to investigate respiratory muscle control

On dynamic network entropy in cancer

The cellular phenotype is described by a complex network of molecular interactions. Elucidating network properties that distinguish disease from the healthy cellular state is therefore of critical importance for gaining systems-level insights into disease mechanisms and ultimately for developing improved therapies. By integrating gene expression data with a protein interaction network to induce a stochastic dynamics on the network, we here demonstrate that cancer cells are characterised by an increase in the dynamic network entropy, compared to cells of normal physiology. Using a fundamental relation between the macroscopic resilience of a dynamical system and the uncertainty (entropy) in the underlying microscopic processes, we argue that cancer cells will be more robust to random gene perturbations. In addition, we formally demonstrate that gene expression differences between normal and cancer tissue are anticorrelated with local dynamic entropy changes, thus providing a systemic link between gene expression changes at the nodes and their local network dynamics. In particular, we also find that genes which drive cell-proliferation in cancer cells and which often encode oncogenes are associated with reductions in the dynamic network entropy. In summary, our results support the view that the observed increased robustness of cancer cells to perturbation and therapy may be due to an increase in the dynamic network entropy that allows cells to adapt to the new cellular stresses. Conversely, genes that exhibit local flux entropy decreases in cancer may render cancer cells more susceptible to targeted intervention and may therefore represent promising drug targets.Comment: 10 pages, 3 figures, 4 tables. Submitte

Physical health complications in children and young people with avoidant restrictive food intake disorder (ARFID): a systematic review and meta-analysis

Background Avoidant restrictive food intake disorder (ARFID) is a feeding and eating disorder with known acute and longstanding physical health complications in children and young people (CYP) and commonly presents to paediatricians. Objective To systematically review the published literature on physical health complications in CYP with ARFID using Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Methods A systematic search of PubMed, Embase, Web of Science, PsycINFO and Cochrane Library was performed on 14 February 2024. Studies reporting physical health complications in CYP ≤25 years with ARFID were included. We pooled studies for meta-analysis comparing ARFID with healthy controls or anorexia nervosa (AN). Results Of 9058 studies found in searches, we included 132 studies. We found evidence for low weight, nutritional deficiencies and low bone mineral density. CYP with ARFID can present across the weight spectrum; however, the majority of CYP with ARFID were within the healthy weight to underweight range. Most studies reported normal range heart rates and blood pressures in ARFID, but some CYP with ARFID do experience bradycardia and hypotension. CYP with ARFID had higher heart rates than AN (weighted mean difference: 12.93 bpm; 95% CI: 8.65 to 17.21; n=685); heterogeneity was high (I2: 81.33%). Conclusion There is a broad range of physical health complications associated with ARFID requiring clinical consideration. Many CYP with ARFID are not underweight yet still have complications. Less cardiovascular complications found in ARFID compared with AN may be related to chronicity

Bioavailability in soils

The consumption of locally-produced vegetables by humans may be an important exposure pathway for soil contaminants in many urban settings and for agricultural land use. Hence, prediction of metal and metalloid uptake by vegetables from contaminated soils is an important part of the Human Health Risk Assessment procedure. The behaviour of metals (cadmium, chromium, cobalt, copper, mercury, molybdenum, nickel, lead and zinc) and metalloids (arsenic, boron and selenium) in contaminated soils depends to a large extent on the intrinsic charge, valence and speciation of the contaminant ion, and soil properties such as pH, redox status and contents of clay and/or organic matter. However, chemistry and behaviour of the contaminant in soil alone cannot predict soil-to-plant transfer. Root uptake, root selectivity, ion interactions, rhizosphere processes, leaf uptake from the atmosphere, and plant partitioning are important processes that ultimately govern the accumulation ofmetals and metalloids in edible vegetable tissues. Mechanistic models to accurately describe all these processes have not yet been developed, let alone validated under field conditions. Hence, to estimate risks by vegetable consumption, empirical models have been used to correlate concentrations of metals and metalloids in contaminated soils, soil physico-chemical characteristics, and concentrations of elements in vegetable tissues. These models should only be used within the bounds of their calibration, and often need to be re-calibrated or validated using local soil and environmental conditions on a regional or site-specific basis.Mike J. McLaughlin, Erik Smolders, Fien Degryse, and Rene Rietr

An online acceptance, commitment, and self-compassion based treatment to decrease psychological distress in people with type 2 diabetes: A feasibility randomised-controlled trial

BACKGROUND AND PURPOSE: This study explored the feasibility and acceptability of conducting a larger trial of a self-guided, online self-compassion and acceptance and commitment therapy (ACT) focused treatment among people with type 2 diabetes (T2D) to decrease psychological distress. MATERIALS AND METHODS: This study was a two-arm, parallel, feasibility randomised controlled trial with nested qualitative methods. UK adults with T2D were randomly (1:1) allocated to a five-week online self-compassion and ACT treatment or waitlist control. Information regarding recruitment, trial retention, and treatment completion was collected, and post-treatment semi-structured interviews were conducted to assess feasibility and acceptability. Self-report measures of psychological distress (depression, anxiety, diabetes distress) and potential treatment processes (self-compassion and psychological flexibility) were completed as secondary feasibility outcomes. RESULTS: Fifty-five (60.44 %) out of 91 people who accessed the study link were eligible to participate. Of these, 33 eligible participants (60 %) were randomly assigned to treatment (n = 19) or control arms (waitlist; n = 14). While treatment completion was 47.37 %, trial retention rates were 39.39 % (5-week follow-up) and 21.2 % (9-week follow-up). Secondary feasibility outcomes of treatment effect estimates are difficult to interpret in light of low treatment completion and trial retention rates. CONCLUSION: A larger trial of the self-guided, online self-compassion treatment to decrease psychological distress in people with T2D may be beneficial, but it has limited feasibility in its current form. Further efforts are needed to improve treatment acceptability of online self-compassion and ACT focused treatment and trial procedures

Systematic review of reviews of symptoms and signs of COVID-19 in children and adolescents

OBJECTIVE: To undertake a systematic review of reviews of the prevalence of symptoms and signs of COVID-19 in those aged under 20 years. DESIGN: Narrative systematic review of reviews. PubMed, medRxiv, Europe PMC and COVID-19 Living Evidence Database were searched on 9 October 2020. SETTING: All settings, including hospitalised and community settings. PATIENTS: Children and young people (CYP) under age 20 years with laboratory-proven COVID-19. STUDY REVIEW, DATA EXTRACTION AND QUALITY: Potentially eligible articles were reviewed on title and abstract by one reviewer. Quality was assessed using the modified AMSTARS criteria and data were extracted from included studies by two reviewers. MAIN OUTCOME MEASURES: Prevalence of symptoms and signs of COVID-19. RESULTS: 1325 studies were identified and 18 reviews were included. Eight were high quality, 7 medium and 3 low quality. All reviews were dominated by studies of hospitalised children. The proportion of asymptomatic CYP ranged from 14.6% to 42%. Fever and cough were the the most common symptoms; proportions with fever ranged from 46% to 64.2% and with cough from 32% to 55.9%. All other symptoms or signs including rhinorrhoea, sore throat, headache, fatigue/myalgia and gastrointestinal symptoms including diarrhoea and vomiting were infrequent, occurring in less than 10%-20%. CONCLUSIONS: Fever and cough are the most common symptoms in CYP with COVID-19, with other symptoms infrequent. Further research on symptoms in community samples are needed to inform pragmatic identification and testing programmes for CYP

Arterial stiffening, insulin resistance and acanthosis nigricans in a community sample of adolescents with obesity.

Acanthosis Nigricans (AN) is a common finding in adolescents with obesity. Little is known about its relevance for cardiovascular (CVS) risk, in particular arterial stiffening. We investigated associations between AN, conventional markers of CVS risk and carotid-radial pulse wave velocity (PWV) in a community sample of adolescents with obesity aged 12-19 recruited to an obesity trial. AN was present in 63% of subjects and 43% had severe grading. Presence of AN and severe AN were associated with z-score of body mass index (BMIz). Presence of AN (but not severity) was associated with abnormal or fasting hyperinsulinaemia but not after adjustment for BMIz. PWV data were available for 147 (84% of participants). Severe-grade AN was associated with PWV (co-efficient 0.51, 95% CI 0.13-0.89, P=0.01) but not when adjusted for BMIz, ethnic grouping and age. In our study presence and severity of AN offered little additional information on CVS risk beyond the degree of obesity itself. The relevance of AN for CVS risk should be interpreted with caution

Alternatives to mental health admissions for children and adolescents experiencing mental health crises: A systematic review of the literature

Background: Many children and young people (CYP) presenting with mental health crises are admitted to hospital due to concerns around illness severity and risk. Whilst inpatient admissions have an important role for such children, there are a number of burdens associated with them, and safe avoidance of admissions is favourable. We systematically reviewed the literature for studies of interventions reported as alternatives to a hospital admission in CYP presenting with mental health crises, in any inpatient setting. Methods: Three databases (PsychInfo, PubMed and Web of Science) were searched for peer-reviewed papers in October 2020, with an updated search in May 2021. Results: We identified 19 papers of interventions delivered in the emergency department, the home, outside of home but outside of clinics and in hospital clinics. The quality of most included studies was low, with less than half being randomised controlled trials and only half of these at low risk of bias. The best quality studies and greatest evidence for efficacy came from in-home interventions, in particular multisystemic therapy, which improved psychological outcomes, and though a large number of CYP still ended up being admitted, there appeared to be decreased length of stay. Conclusions: Overall, we could not recommend a particular intervention as an alternative to inpatient admission; however, our review describes benefits across a range of types of interventions that might be considered in multi-modal treatments. We also provide recommendations for future research, in particular the evaluation of new interventions as they emerge

User Experiences of Development of Dependence on the Synthetic Cannabinoids, 5f-AKB48 and 5F-PB-22, and Subsequent Withdrawal Syndromes

Emergence of synthetic cannabinoids (SCBs) in herbal smoking mixtures is a public health concern. New SCB’s such as 5f-AKB48 and 5F-PB-22 have been detected in French seizures and in sudden death post mortems in the US. The aim was to describe development of dependence on herbal smoking mixtures containing the SCB’s, 5f-AKB48 and 5F-PB-22 and subsequent withdrawal syndromes. Dependent users of herbal smoking mixtures known to contain the SCB’s 5f-AKB48 and 5F-PB-22 with an average Severity of Dependence Score (SDS) of 13 were interviewed using a structured guide (three males/three females). Narratives were analysed using the Empirical Phenomenological Psychological (EPP) five step method. Six themes with 68 categories emerged from the analysis. Themes are illustrated as 1) Networks and Product Availability; 2) Drivers and Motives for Use; 3) Effect and Pathways toward Dependence; 4) Poly Substance Use and Comparisons to Natural Cannabis; 5) Dependence and Withdrawal and 6) Self-detoxification Attempts. Two higher levels of abstraction above these theme-levels emerged from the data, with sole use of herbal smoking mixtures containing 5f-AKB48 and 5F-PB-22 centering on the interplay between intense cravings, compulsive all-consuming seeking, use and re-dose behaviours, and fear of the psychiatric and self-harms caused when in withdrawal. This is the first study describing dependence and withdrawal experiences in users dependent on 5f-AKB48 and 5F-PB-22. Given the potential for adverse psychiatric and physical consequences of dependent use, further development of specific clinical responses and clinical research around toxicity and withdrawal severity are warranted